In response to RFA DA-10-017-Seek, Test & Treat: Addressing HIV in the Criminal Justice System, we propose to determine if a comprehensive program based on elements of seek-test-and-treat results in a significant reduction in the potential for HIV-infected prisoners to transmit their virus after release. We have assembled a multiple institutional, multi-disciplinary, multiple PI research team with extensive experience conducting significant and innovative research in the North Carolina (NC) and Texas (TX) criminal justice systems which collectively represent 15% of all persons in US state prisons. Our proposal capitalizes on existing strengths in these correctional systems - mandatory or opt-out HIV testing, and universal ART access, with resulting strong viral suppression - while targeting key vulnerabilities identified in the test-and-treat paradigm for these populations: 1) client engagement and participation in HIV care, 2) systematic screening for ancillary needs and rapid personalized linkage to outside HIV care, and 3) supportive services (e.g., mental health and substance abuse) critical to sustaining treatment engagement for this complex population. We will adapt and integrate existing interventions to enhance ART adherence and utilization of care to create a multi-component intervention for prisoners in NC and TX; compare the effect of standard prison practice with this multicomponent intervention using a randomized control trial design with 514 HIV-infected inmates by testing a primary outcome of the proportion in each study arm with an HIV RNA level <400 c/mL at week 36 post-randomization (~24 weeks after release); and describe and model secondary outcomes (e.g., post-release HIV transmission risk behaviors, incident STIs, adherence to ART, medical care appointments, emergence of ART resistance mutations, and predicted HIV transmission events). The proposed research represents one of the largest and most rigorous studies of risk behavior among a cohort of HIV-infected releasees ever undertaken. Innovations include the use of self-reported risk assessed via ACASI, detecting incident STIs through urine specimens, HIV genotypic resistance testing for those with post-release HIV RNA levels >1,000 c/mL allowing us to identify the development of new drug resistance mutations, use of audio-visual media in prisons, and use of cellular phones to deliver Motivational Interviewing sessions post-release, to conduct unannounced pill counts, and deliver audio files and text messages including tailored reminders regarding ART dosing and HIV-related clinic appointments following release. The proposal addresses a highly significant public health issue with potential to greatly advance the US HIV prevention agenda by delivering and testing a comprehensive intervention to sustain HIV viral suppression. PUBLIC HEALTH RELEVANCE: This application targets a group with a relatively high potential to transmit HIV-infected prisoners after their release. These individuals shoulder a burden of HIV several fold greater than that of the general population, and a significant proportion of HIV-infected Americans are incarcerated. The aims of this application address persistent suppression of HIV viremia and reduced propensity to transmit HIV by prisoners after their release, thus the proposed research addresses a highly significant public health issue and has great potential to advance the US HIV prevention agenda.